How to cite this article:Dabholkar J. Is human papilloma virus positivity in oropharyngeal cancers a game changer in Indian subcontinent?. J Head Neck Physicians Surg 2017;5:1-2

How to cite this URL:Dabholkar J. Is human papilloma virus positivity in oropharyngeal cancers a game changer in Indian subcontinent?. J Head Neck Physicians Surg [serial online] 2017 [cited 2020 Jun 7];5:1-2. Available from: http://www.jhnps.org/text.asp?2017/5/1/1/211726

The rising incidence of oropharyngeal carcinoma and their relationship with human papilloma virus (HPV) has been alarming in the last decade. HPV-induced oropharyngeal carcinoma have been defined as a different subset with improved prognosis.[1] The latest AJCC 8th edition[2] and NCCN guideline 2017[3] have divided the oropharyngeal carcinoma and pathological nodal staging separately compared to HPV negative carcinoma emphasizing over the fact that HPV positivity is a good prognostic factor and a game changer in the realm of oropharyngeal carcinoma. This is very true for the Western world and their changing population subset of younger nonsmoking patients with oropharyngeal cancer. However, the point to ponder on whether HPV actually a gamer changer in Indian scenario??

First, the incidence of HPV-induced oropharyngeal carcinoma is debatable in the case of the Indian subcontinent with the majority of patients with oropharyngeal cancer had a history of tobacco abuse in the form of chewable tobacco or smoking beedis/cigarettes. Data from Centers for Disease Control and Prevention, USA found the significant disparity in prevalence of HPV between various racial groups in the USA. They found that among american white people, 82 men per million suffered from HPV-induced oropharyngeal cancer compared to Asian group which had only 20 men per million suffering from HPV-induced oropharyngeal cancer in the USA.[4]

The other debate with the advent of HPV is the de-intensification of treatment. To start with, there were reports of HPV-induced oropharyngeal malignancy having a better response to the accepted line of management of chemoradiation. Hence, it was proposed to deintensify the treatment for this group of patients with scaling down to radical radiotherapy rather than chemoradiotherapy and feasibility of reducing the dosage of radiotherapy. Ang et al.[5] found that intermediate risk group with a history of smoking <10 pack years with HPV positive oropharyngeal cancer with the N2c-N3 nodal disease have a similar outcome as that of HPV negative oropharyngeal carcinoma with more than 10 pack year of smoking. Similarly, O'Sullivan et al.[6] compared treatment in HPV negative and HPV positive patients. They found that 3 years disease-free survival in both high- and low-risk groups in HPV positive and HPV negative cancer were very similar (93% vs. 93% and 72% vs. 76%, respectively). They also found that HPV positive patient had a chance of distant metastasis up to 5 years posttreatment compared 2 years in HPV negative patient.[7] On the other hand, the ECOG-ACRIN phase II E1308 trial in which patients with stage III–IV HPV16 and/or p16-positive oropharyngeal cancer with 80 patients received induction chemotherapy followed by reduced-dose radiation therapy (RT) and weekly cetuximab reported results showing that RT de-intensification may result in equivalent or similar responses in selected patients compared with full-dose RT.[8] Most of the protagonist have used the retrospective data with drawbacks of having short follow up period and questionable method of HPV testing.

There has also been a debate on the significance of nodal burden and extracapsular spread in HPV positive cancer. Sinha et al.[9] in their prospective study of 220 patients of HPV positive oropharyngeal cancers found that a number of metastatic nodes, not extracapsular spread or high N-classification are an independent predictor of outcomes in surgically-treated HPV positive oropharyngeal cancer patients. They also concluded that patient with more than 5 metastatic nodes should be followed up more intensely due to a higher risk of disease relapse even if the disease-specific survival was up to the tune of 80%. AJCC 8th edition has also classified pathological staging in pN1 with <4 positive nodes and pN2 being 5 or more metastatic nodes, but clinical classification still takes size and side in consideration.

Another debate is over the usefulness of the preventive measure (HPV vaccine). Opinion is divided about HPV vaccine prophylaxis and the age group in which should be administered to prevent oropharyngeal carcinoma. A general consensus about the age group of 14–18 years (both male and female) should be administered the vaccine. Herrero et al.[10] conducted a randomized trial with over 7000 female patients and administered HPV vaccine and used Hepatitis A vaccine as control. They found that at the end of 4 years, the prevalence of oral HPV was only 1.7% in the HPV vaccinated group and the vaccine efficiency was found to be 93%. There is still need to assess the efficacy of the vaccine in an overall reduction of incidence of oropharyngeal carcinoma and its cost effectiveness in the Indian subcontinent.

To conclude, there is a lack of systematic prospective study to quantify the burden of oropharyngeal cancers due to HPV in the Indian subcontinent. The biggest hurdle in the scenario will be an overlap of HPV positivity with a history of significant tobacco abuse which is predominant in the Indian subcontinent. There is a need of phase III study in the form of randomized trials with 5–10 years follow up to ascertain the feasibility of deintensitfication of treatment and intensity of follow up. There has been proof that HPV vaccine reduces the oral HPV prevalence but will that be effective enough to reduce the incidence of oropharyngeal carcinoma in our country is still to be proven. Detection of HPV in oropharyngeal cancer case is definitely a good prognostic factor, but it being a game changer in Indian scenario is debatable and yet to be supported by evidence.